Identification of a conserved chemokine receptor motif that enables ligand discrimination
Sci Signal. 2022 Mar 8;15(724):eabg7042. doi: 10.1126/scisignal.abg7042. Epub 2022 Mar 8.ABSTRACTExtensive ligand-receptor promiscuity in the chemokine signaling system balances beneficial redundancy and specificity. However, this feature poses a major challenge to selectively modulate the system pharmacologically. Here, we identified a conserved cluster of three aromatic receptor residues that anchors the second extracellular loop (ECL2) to the top of receptor transmembrane helices (TM) 4 and 5 and enables recognition of both shared and specific characteristics of interacting chemokines. This cluster was essential for the...
Source: Science Signaling - March 8, 2022 Category: Biomedical Science Authors: Olav Larsen Wijnand J C van der Velden Ma ša Mavri Sara Schuermans Pia C Rummel Stefanie Karlsh øj Martin Gustavsson Paul Proost Jon V åbenø Mette M Rosenkilde Source Type: research

The suppressive effects of Mer inhibition on inflammatory responses in the pathogenesis of LPS-induced ALI/ARDS
Sci Signal. 2022 Mar 8;15(724):eabd2533. doi: 10.1126/scisignal.abd2533. Epub 2022 Mar 8.ABSTRACTThe pathogenesis of sepsis-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) has not yet been fully elucidated. Growth arrest-specific 6 (Gas6) has marked effects on hemostasis and reduces inflammation through its interaction with receptor tyrosine kinases of the TAM family: Tyro3, Axl, and Mer. Here, we found that plasma concentrations of Gas6 and soluble Mer were greater in patients with severe sepsis or septic ALI/ARDS compared with those in normal healthy donors. To determine whether the Gas6-Mer ax...
Source: Science Signaling - March 8, 2022 Category: Biomedical Science Authors: Masahiko Fukatsu Hiroshi Ohkawara Xintao Wang Lobna Alkebsi Miki Furukawa Hirotaka Mori Miwa Fukami Shin-Ichi Fukami Takahiro Sano Hiroshi Takahashi Kayo Harada-Shirado Satoshi Kimura Koichi Sugimoto Kazuei Ogawa Takayuki Ikezoe Source Type: research

Fibrous stroma: Driver and passenger in cancer development
Sci Signal. 2022 Mar 8;15(724):eabg3449. doi: 10.1126/scisignal.abg3449. Epub 2022 Mar 8.ABSTRACTCumulative evidence shows that fibrogenic stroma and stiff extracellular matrix (ECM) not only result from tumor growth but also play pivotal roles in cellular transformation and tumor initiation. This emerging concept may largely account for the increased cancer risk associated with environmental fibrogenic agents, such as asbestos and silica, and with chronic conditions that are fibrogenic, such as obesity and diabetes. It may also contribute to poor outcomes in patients treated with certain chemotherapeutics that can promote...
Source: Science Signaling - March 8, 2022 Category: Biomedical Science Authors: Vandana Sharma Joshua Letson Saori Furuta Source Type: research

A mutation breaks its silence on mutant KRAS
Sci Signal. 2022 Mar 8;15(724):eabp8972. doi: 10.1126/scisignal.abp8972. Epub 2022 Mar 8.ABSTRACTLeveraging silent mutations and alternative splicing enables targeting of a KRAS mutant.PMID:35258996 | DOI:10.1126/scisignal.abp8972 (Source: Science Signaling)
Source: Science Signaling - March 8, 2022 Category: Biomedical Science Authors: Amy E Baek Source Type: research

Identification of a conserved chemokine receptor motif that enables ligand discrimination
Sci Signal. 2022 Mar 8;15(724):eabg7042. doi: 10.1126/scisignal.abg7042. Epub 2022 Mar 8.ABSTRACTExtensive ligand-receptor promiscuity in the chemokine signaling system balances beneficial redundancy and specificity. However, this feature poses a major challenge to selectively modulate the system pharmacologically. Here, we identified a conserved cluster of three aromatic receptor residues that anchors the second extracellular loop (ECL2) to the top of receptor transmembrane helices (TM) 4 and 5 and enables recognition of both shared and specific characteristics of interacting chemokines. This cluster was essential for the...
Source: Science Signaling - March 8, 2022 Category: Biomedical Science Authors: Olav Larsen Wijnand J C van der Velden Ma ša Mavri Sara Schuermans Pia C Rummel Stefanie Karlsh øj Martin Gustavsson Paul Proost Jon V åbenø Mette M Rosenkilde Source Type: research

The suppressive effects of Mer inhibition on inflammatory responses in the pathogenesis of LPS-induced ALI/ARDS
Sci Signal. 2022 Mar 8;15(724):eabd2533. doi: 10.1126/scisignal.abd2533. Epub 2022 Mar 8.ABSTRACTThe pathogenesis of sepsis-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) has not yet been fully elucidated. Growth arrest-specific 6 (Gas6) has marked effects on hemostasis and reduces inflammation through its interaction with receptor tyrosine kinases of the TAM family: Tyro3, Axl, and Mer. Here, we found that plasma concentrations of Gas6 and soluble Mer were greater in patients with severe sepsis or septic ALI/ARDS compared with those in normal healthy donors. To determine whether the Gas6-Mer ax...
Source: Science Signaling - March 8, 2022 Category: Biomedical Science Authors: Masahiko Fukatsu Hiroshi Ohkawara Xintao Wang Lobna Alkebsi Miki Furukawa Hirotaka Mori Miwa Fukami Shin-Ichi Fukami Takahiro Sano Hiroshi Takahashi Kayo Harada-Shirado Satoshi Kimura Koichi Sugimoto Kazuei Ogawa Takayuki Ikezoe Source Type: research

Fibrous stroma: Driver and passenger in cancer development
Sci Signal. 2022 Mar 8;15(724):eabg3449. doi: 10.1126/scisignal.abg3449. Epub 2022 Mar 8.ABSTRACTCumulative evidence shows that fibrogenic stroma and stiff extracellular matrix (ECM) not only result from tumor growth but also play pivotal roles in cellular transformation and tumor initiation. This emerging concept may largely account for the increased cancer risk associated with environmental fibrogenic agents, such as asbestos and silica, and with chronic conditions that are fibrogenic, such as obesity and diabetes. It may also contribute to poor outcomes in patients treated with certain chemotherapeutics that can promote...
Source: Science Signaling - March 8, 2022 Category: Biomedical Science Authors: Vandana Sharma Joshua Letson Saori Furuta Source Type: research

A mutation breaks its silence on mutant KRAS
Sci Signal. 2022 Mar 8;15(724):eabp8972. doi: 10.1126/scisignal.abp8972. Epub 2022 Mar 8.ABSTRACTLeveraging silent mutations and alternative splicing enables targeting of a KRAS mutant.PMID:35258996 | DOI:10.1126/scisignal.abp8972 (Source: Science Signaling)
Source: Science Signaling - March 8, 2022 Category: Biomedical Science Authors: Amy E Baek Source Type: research

Identification of a conserved chemokine receptor motif that enables ligand discrimination
Sci Signal. 2022 Mar 8;15(724):eabg7042. doi: 10.1126/scisignal.abg7042. Epub 2022 Mar 8.ABSTRACTExtensive ligand-receptor promiscuity in the chemokine signaling system balances beneficial redundancy and specificity. However, this feature poses a major challenge to selectively modulate the system pharmacologically. Here, we identified a conserved cluster of three aromatic receptor residues that anchors the second extracellular loop (ECL2) to the top of receptor transmembrane helices (TM) 4 and 5 and enables recognition of both shared and specific characteristics of interacting chemokines. This cluster was essential for the...
Source: Science Signaling - March 8, 2022 Category: Biomedical Science Authors: Olav Larsen Wijnand J C van der Velden Ma ša Mavri Sara Schuermans Pia C Rummel Stefanie Karlsh øj Martin Gustavsson Paul Proost Jon V åbenø Mette M Rosenkilde Source Type: research

The suppressive effects of Mer inhibition on inflammatory responses in the pathogenesis of LPS-induced ALI/ARDS
Sci Signal. 2022 Mar 8;15(724):eabd2533. doi: 10.1126/scisignal.abd2533. Epub 2022 Mar 8.ABSTRACTThe pathogenesis of sepsis-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) has not yet been fully elucidated. Growth arrest-specific 6 (Gas6) has marked effects on hemostasis and reduces inflammation through its interaction with receptor tyrosine kinases of the TAM family: Tyro3, Axl, and Mer. Here, we found that plasma concentrations of Gas6 and soluble Mer were greater in patients with severe sepsis or septic ALI/ARDS compared with those in normal healthy donors. To determine whether the Gas6-Mer ax...
Source: Science Signaling - March 8, 2022 Category: Biomedical Science Authors: Masahiko Fukatsu Hiroshi Ohkawara Xintao Wang Lobna Alkebsi Miki Furukawa Hirotaka Mori Miwa Fukami Shin-Ichi Fukami Takahiro Sano Hiroshi Takahashi Kayo Harada-Shirado Satoshi Kimura Koichi Sugimoto Kazuei Ogawa Takayuki Ikezoe Source Type: research

Fibrous stroma: Driver and passenger in cancer development
Sci Signal. 2022 Mar 8;15(724):eabg3449. doi: 10.1126/scisignal.abg3449. Epub 2022 Mar 8.ABSTRACTCumulative evidence shows that fibrogenic stroma and stiff extracellular matrix (ECM) not only result from tumor growth but also play pivotal roles in cellular transformation and tumor initiation. This emerging concept may largely account for the increased cancer risk associated with environmental fibrogenic agents, such as asbestos and silica, and with chronic conditions that are fibrogenic, such as obesity and diabetes. It may also contribute to poor outcomes in patients treated with certain chemotherapeutics that can promote...
Source: Science Signaling - March 8, 2022 Category: Biomedical Science Authors: Vandana Sharma Joshua Letson Saori Furuta Source Type: research

A mutation breaks its silence on mutant KRAS
Sci Signal. 2022 Mar 8;15(724):eabp8972. doi: 10.1126/scisignal.abp8972. Epub 2022 Mar 8.ABSTRACTLeveraging silent mutations and alternative splicing enables targeting of a KRAS mutant.PMID:35258996 | DOI:10.1126/scisignal.abp8972 (Source: Science Signaling)
Source: Science Signaling - March 8, 2022 Category: Biomedical Science Authors: Amy E Baek Source Type: research

Identification of a conserved chemokine receptor motif that enables ligand discrimination
Sci Signal. 2022 Mar 8;15(724):eabg7042. doi: 10.1126/scisignal.abg7042. Epub 2022 Mar 8.ABSTRACTExtensive ligand-receptor promiscuity in the chemokine signaling system balances beneficial redundancy and specificity. However, this feature poses a major challenge to selectively modulate the system pharmacologically. Here, we identified a conserved cluster of three aromatic receptor residues that anchors the second extracellular loop (ECL2) to the top of receptor transmembrane helices (TM) 4 and 5 and enables recognition of both shared and specific characteristics of interacting chemokines. This cluster was essential for the...
Source: Science Signaling - March 8, 2022 Category: Biomedical Science Authors: Olav Larsen Wijnand J C van der Velden Ma ša Mavri Sara Schuermans Pia C Rummel Stefanie Karlsh øj Martin Gustavsson Paul Proost Jon V åbenø Mette M Rosenkilde Source Type: research

The suppressive effects of Mer inhibition on inflammatory responses in the pathogenesis of LPS-induced ALI/ARDS
Sci Signal. 2022 Mar 8;15(724):eabd2533. doi: 10.1126/scisignal.abd2533. Epub 2022 Mar 8.ABSTRACTThe pathogenesis of sepsis-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) has not yet been fully elucidated. Growth arrest-specific 6 (Gas6) has marked effects on hemostasis and reduces inflammation through its interaction with receptor tyrosine kinases of the TAM family: Tyro3, Axl, and Mer. Here, we found that plasma concentrations of Gas6 and soluble Mer were greater in patients with severe sepsis or septic ALI/ARDS compared with those in normal healthy donors. To determine whether the Gas6-Mer ax...
Source: Science Signaling - March 8, 2022 Category: Biomedical Science Authors: Masahiko Fukatsu Hiroshi Ohkawara Xintao Wang Lobna Alkebsi Miki Furukawa Hirotaka Mori Miwa Fukami Shin-Ichi Fukami Takahiro Sano Hiroshi Takahashi Kayo Harada-Shirado Satoshi Kimura Koichi Sugimoto Kazuei Ogawa Takayuki Ikezoe Source Type: research

Fibrous stroma: Driver and passenger in cancer development
Sci Signal. 2022 Mar 8;15(724):eabg3449. doi: 10.1126/scisignal.abg3449. Epub 2022 Mar 8.ABSTRACTCumulative evidence shows that fibrogenic stroma and stiff extracellular matrix (ECM) not only result from tumor growth but also play pivotal roles in cellular transformation and tumor initiation. This emerging concept may largely account for the increased cancer risk associated with environmental fibrogenic agents, such as asbestos and silica, and with chronic conditions that are fibrogenic, such as obesity and diabetes. It may also contribute to poor outcomes in patients treated with certain chemotherapeutics that can promote...
Source: Science Signaling - March 8, 2022 Category: Biomedical Science Authors: Vandana Sharma Joshua Letson Saori Furuta Source Type: research